Psychopharmacology

, Volume 198, Issue 2, pp 261–270 | Cite as

Intracranial self-administration of MDMA into the ventral striatum of the rat: differential roles of the nucleus accumbens shell, core, and olfactory tubercle

  • Rick Shin
  • Mei Qin
  • Zhong-Hua Liu
  • Satoshi Ikemoto
Original Investigation

Abstract

Rationale

Behavioral and anatomical data suggest that the ventral striatum, consisting of the nucleus accumbens and olfactory tubercle, is functionally heterogeneous. Cocaine and d-amphetamine appear to be more rewarding when administered into the medial olfactory tubercle or medial accumbens shell than into their lateral counterparts, including the accumbens core.

Objectives

We sought to determine whether rats self-administer the popular recreational drug (±)-3,4-methylenedioxymethamphetamine (MDMA) into ventrostriatal subregions and whether the medial olfactory tubercle and medial accumbens shell mediate MDMA’s positive reinforcing effects more effectively than their lateral counterparts.

Results

Rats receiving 30 mM MDMA into the medial olfactory tubercle, medial accumbens shell, or accumbens core, but not the lateral tubercle or lateral shell, showed higher self-administration rates than rats receiving vehicle. The medial shell supported more vigorous self-administration of MDMA at higher concentrations than the core or medial olfactory tubercle. In addition, intra-medial shell MDMA self-administration was disrupted by co-administration of the D1 or D2 receptor antagonists SCH 23390 (1–3 mM) or raclopride (3–10 mM).

Conclusions

Our data suggest that the ventral striatum is functionally heterogeneous. The medial accumbens shell appears to be more important than other ventrostriatal subregions in mediating the positive reinforcing effects of MDMA via both D1- and D2-type receptors. Together with previous data, our data also suggest that unidentified actions of MDMA interfere with the positive reinforcing effects of dopamine in the medial olfactory tubercle.

Keywords

Intracranial self-administration Reward Reinforcement Ecstasy Dopamine Nucleus accumbens Core Shell D1 receptors D2 receptors 

References

  1. Bari AA, Pierce RC (2005) D1-like and D2 dopamine receptor antagonists administered into the shell subregion of the rat nucleus accumbens decrease cocaine, but not food, reinforcement. Neuroscience 135:959–968PubMedCrossRefGoogle Scholar
  2. Bossert JM, Poles GC, Wihbey KA, Koya E, Shaham Y (2007) Differential effects of blockade of dopamine D1-family receptors in nucleus accumbens core or shell on reinstatement of heroin seeking induced by contextual and discrete cues. J Neurosci 27:12655–12663PubMedCrossRefGoogle Scholar
  3. Carlezon WA Jr, Devine DP, Wise RA (1995) Habit-forming actions of nomifensine in nucleus accumbens. Psychopharmacology 122:194–197PubMedCrossRefGoogle Scholar
  4. Daniela E, Brennan K, Gittings D, Hely L, Schenk S (2004) Effect of SCH 23390 on (+/−)-3,4-methylenedioxymethamphetamine hyperactivity and self-administration in rats. Pharmacol Biochem Behav 77:745–750PubMedCrossRefGoogle Scholar
  5. De La Garza R 2nd, Fabrizio KR, Gupta A (2007) Relevance of rodent models of intravenous MDMA self-administration to human MDMA consumption patterns. Psychopharmacology (Berl) 189:425–434CrossRefGoogle Scholar
  6. Fenu S, Spina L, Rivas E, Longoni R, Di Chiara G (2006) Morphine-conditioned single-trial place preference: role of nucleus accumbens shell dopamine receptors in acquisition, but not expression. Psychopharmacology (Berl) 187:143–153CrossRefGoogle Scholar
  7. Fibiger HC, Phillips AG (1986) Reward, motivation, cognition: psychobiology of mesotelencephalic dopamine systems. In: Mountcastle VB, Bloom FE, Geiger SR (eds) Handbook of physiology: vol. 4. The nervous system. American Physiological Society, Bethesda, pp 647–675Google Scholar
  8. Green AR, Mechan AO, Elliott JM, O’Shea E, Colado MI (2003) The pharmacology and clinical pharmacology of 3,4-methylenedioxymethamphetamine (MDMA, “ecstasy”). Pharmacol Rev 55:463–508PubMedCrossRefGoogle Scholar
  9. Ikemoto S (2003) Involvement of the olfactory tubercle in cocaine reward: intracranial self-administration studies. J Neurosci 23:9305–9311PubMedGoogle Scholar
  10. Ikemoto S (2007) Dopamine reward circuitry: two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex. Brain Res Rev 56:27–78PubMedCrossRefGoogle Scholar
  11. Ikemoto S, Sharpe LG (2001) A head-attachable device for injecting nanoliter volumes of drug solutions into brain sites of freely moving rats. J Neurosci Methods 110:135–140PubMedCrossRefGoogle Scholar
  12. Ikemoto S, Wise RA (2004) Mapping of chemical trigger zones for reward. Neuropharmacology 47:190–201PubMedCrossRefGoogle Scholar
  13. Ikemoto S, Glazier BS, Murphy JM, McBride WJ (1997) Role of dopamine D1 and D2 receptors in the nucleus accumbens in mediating reward. J Neurosci 17:8580–8587PubMedGoogle Scholar
  14. Ikemoto S, Qin M, Liu ZH (2005) The functional divide for primary reinforcement of D-amphetamine lies between the medial and lateral ventral striatum: is the division of the accumbens core, shell and olfactory tubercle valid. J Neurosci 25:5061–5065PubMedCrossRefGoogle Scholar
  15. Ito R, Robbins TW, Everitt BJ (2004) Differential control over cocaine-seeking behavior by nucleus accumbens core and shell. Nat Neurosci 7:389–397PubMedCrossRefGoogle Scholar
  16. Kankaanpaa A, Meririnne E, Lillsunde P, Seppala T (1998) The acute effects of amphetamine derivatives on extracellular serotonin and dopamine levels in rat nucleus accumbens. Pharmacol Biochem Behav 59:1003–1009PubMedCrossRefGoogle Scholar
  17. Koob GF (1992) Drugs of abuse: anatomy, pharmacology and function of reward pathways. Trends Pharmacol Sci 13:177–184PubMedCrossRefGoogle Scholar
  18. McBride WJ, Murphy JM, Ikemoto S (1999) Localization of brain reinforcement mechanisms: intracranial self-administration and intracranial place-conditioning studies. Behav Brain Res 101:129–152PubMedCrossRefGoogle Scholar
  19. Parrott AC (2001) Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research. Hum Psychopharmacol 16:557–577PubMedCrossRefGoogle Scholar
  20. Parrott AC (2004) Is ecstasy MDMA? A review of the proportion of ecstasy tablets containing MDMA, their dosage levels, and the changing perceptions of purity. Psychopharmacology (Berl) 173:234–241CrossRefGoogle Scholar
  21. Paxinos G, Watson C (2005) The rat brain in stereotaxic coordinates. Elsevier, BurlingtonGoogle Scholar
  22. Pierce RC, Kumaresan V (2006) The mesolimbic dopamine system: the final common pathway for the reinforcing effect of drugs of abuse. Neurosci Biobehav Rev 30:215–238PubMedCrossRefGoogle Scholar
  23. Pope HG Jr, Ionescu-Pioggia M, Pope KW (2001) Drug use and life style among college undergraduates: a 30-year longitudinal study. Am J Psychiatry 158:1519–1521PubMedCrossRefGoogle Scholar
  24. Rodd-Henricks ZA, McKinzie DL, Li TK, Murphy JM, McBride WJ (2002) Cocaine is self-administered into the shell but not the core of the nucleus accumbens of Wistar rats. J Pharmacol Exp Ther 303:1216–1226PubMedCrossRefGoogle Scholar
  25. Rothman RB, Baumann MH, Dersch CM, Romero DV, Rice KC, Carroll FI, Partilla JS (2001) Amphetamine-type central nervous system stimulants release norepinephrine more potently than they release dopamine and serotonin. Synapse 39:32–41PubMedCrossRefGoogle Scholar
  26. Sellings LH, Clarke PB (2003) Segregation of amphetamine reward and locomotor stimulation between nucleus accumbens medial shell and core. J Neurosci 23:6295–6303PubMedGoogle Scholar
  27. Sellings LH, McQuade LE, Clarke PB (2006a) Characterization of dopamine-dependent rewarding and locomotor stimulant effects of intravenously-administered methylphenidate in rats. Neuroscience 141:1457–1468PubMedCrossRefGoogle Scholar
  28. Sellings LH, McQuade LE, Clarke PB (2006b) Evidence for multiple sites within rat ventral striatum mediating cocaine conditioned place preference and locomotor activation. J Pharmacol Exp Ther 317:1178–1187PubMedCrossRefGoogle Scholar
  29. Spina L, Fenu S, Longoni R, Rivas E, Di Chiara G (2006) Nicotine-conditioned single-trial place preference: selective role of nucleus accumbens shell dopamine D1 receptors in acquisition. Psychopharmacology (Berl) 184:447–455CrossRefGoogle Scholar
  30. White SR, Obradovic T, Imel KM, Wheaton MJ (1996) The effects of methylenedioxymethamphetamine (MDMA, “Ecstasy”) on monoaminergic neurotransmission in the central nervous system. Prog Neurobiol 49:455–479PubMedCrossRefGoogle Scholar
  31. Wise RA, Bozarth MA (1987) A psychomotor stimulant theory of addiction. Psychol Rev 94:469–492PubMedCrossRefGoogle Scholar
  32. Yamamoto BK, Spanos LJ (1988) The acute effects of methylenedioxymethamphetamine on dopamine release in the awake-behaving rat. Eur J Pharmacol 148:195–203PubMedCrossRefGoogle Scholar

Copyright information

© US Government 2008

Authors and Affiliations

  • Rick Shin
    • 1
  • Mei Qin
    • 1
  • Zhong-Hua Liu
    • 1
  • Satoshi Ikemoto
    • 1
  1. 1.Behavioral Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of HealthUS Department of Health and Human ServicesBaltimoreUSA

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